Knockdown of LncRNA CRNDE suppresses proliferation and P-glycoprotein-mediated multidrug resistance in acute myelocytic leukemia through the Wnt/β-catenin pathway.

: Mechanisms involving in noncoding RNAs have been implicated in multidrug resistance (MDR) of acute myeloid leukemia (AML). LncRNA CRNDE (CRNDE) was reported to be involved in the malignant progression in AML. The purpose of this study is to explore the roles and potential molecular mechanism of CRNDE in the MDR in AML. In our study, we confirmed that the expression of CRNDE was significantly upregulated in patients with AML, especially in AML patients after ADR-based chemotherapy. Spearman correlation analysis showed a positive correlation between the levels of CRNDE and MDR1 in AML patients after ADR-based chemotherapy. Moreover, CRNDE was upregulated in AML cells, especially in ADR-resistant AML cells. MDR1/P-gp levels were significantly increased in ADR-resistant AML cells, compared with parental AML cells. CRNDE downregulation inhibited cell proliferation, promoted apoptosis, reduced Ki67 expression and enhanced cleaved caspase-3 expression in AML and ADR-resistant AML cells. In addition, CRNDE knockdown led to downregulation of P-gp/MRP1, β-catenin, c-Myc and cyclinD1 expression, and enhanced the drug-sensitivity to ADR in ADR-resistant AML cells. In conclusion, knockdown of CRNDE suppresses proliferation and P-g-mediated MDR in ADR-resistant AML cells via inhibiting the Wnt/β-catenin pathway, suggesting that repression of CRNDE might be a therapeutic target to reverse MDR of ADR-resistant AML cells.